The present invention is in the field of pharmacotherapy. More specifically, it relates to the treatment of diseases and conditions affecting the skin and skin appendages.
The pharmacological treatment of cutaneous disorders may involve systemic or local administration of an effective medicament. Typically, whenever local (e.g. epicutaneous) administration is possible and leads to the desired outcome, it is preferred over systemic therapy which is, quite plausibly, more often associated with adverse systemic effects. However, effective treatment via the topical route of administration requires that the drug substance is soluble in, and/or otherwise compatible with a suitable carrier or vehicle, and that it reaches its target tissue layer(s) in an effective amount or concentration. In fact, in some cases, effective epicutaneous treatment is particularly difficult to achieve.
The skin consists of three main layers—the epidermis, the dermis and the hypodermis. The epidermis comprises the stratum corneum (the outermost superficial layer of skin, consisting of dead cells) and the vital (living) epidermis. Depending on the cutaneous disease or condition, one or more layers of the skin may become affected. In some dermatological conditions, such as ichthyosis, callus, or plaque psoriasis, the stratum corneum is thicker than in the healthy state and can provide a significantly greater barrier to the penetration of a therapeutical compound, thus reducing its efficacy in the treatment of the deeper layers of the skin. Moreover, it has been shown recently that with increasing age, the skin of a human also becomes more resistant to the penetration by drug substances.
The use of penetration enhancers has been proposed in order to achieve a sufficient and consistent availability of various therapeutic compounds at the site of action during the treatment of cutaneous diseases. For example, U.S. Pat. No. 5,326,566 describes a composition of a pharmacological agent in combination with dibutyl adipate, or a mixture of dibutyl adipate and isopropyl myristate, which could enhance the penetration through the skin and even increase the amount absorbed into the systemic circulation, if that is desired.
Even though a variety of penetration enhancers have been used for enhancing the absorption of therapeutic agents into and through the skin, substantial problems may arise when the penetration enhancers are incompatible with a particular drug substance, leading to drug instability and degradation into potentially harmful degradants.
US 2005/0079210 A1 proposes the use of liposomes the epicutaneous administration of drugs and cosmetically useful agents. However, liposomes are difficult to manufacture cost-effectively and in a reproducible manner.
Other novel formulation strategies for topical medications require the occlusion of the skin after administration, which is however perceived as inconvenient by many patients
EP0670159A1 discloses stable oily emulsions comprising surfactant and semifluorinated alkane, which are proposed to be suitable for transporting oxygen to the skin or vascular system or for use as a standard for blood-gas analysis. The use of these compositions as carriers of active agent was also suggested, although no mention is made of whether these compositions are capable of effectively delivering active agents in particular to the deeper layers of the skin.
There clearly remains a need for pharmaceutical formulations and vehicles which allow the effective treatment of cutaneous disorders by topical administration. It is therefore an object of the present invention to provide such improved compositions which overcome one or more disadvantages of known compositions. In particular, it is an object of the invention to provide compositions of topically active drug substances which are effective and convenient. Further objects of the invention will become clear on the basis of the description of the invention below, including the examples, and of the patent claims.